aminoglycoside 2

Aminoglycoside

Introduction

These are a group of natural and semisynthetic antibiotics having polybasic amino groups linked

glycosidically to two or more aminosugar (streptidine, 2-deoxy streptamine, garosamine )

residues.

Unlike penicillin, which was a chance discovery, aminoglycosides are products of

deliberate search for drug effective against gram –negative bacteria. Streptomycin was the first

member discovered in 1944 by Waksman and his colleagues. It assumed gread importance

because it was active against tuberclebacilli. Others have been produced later, now

aminoglycosides are a sizable family. All aminoglycosides are produced by soil actinomycetes

and have many common properties

An aminoglycoside is a molecule or a portion of a molecule composed of amino-modified

sugars[1]

Several aminoglycosides function as antibiotics that are effective against certain types of

bacteria. They include amikacin, arbekacin, gentamicin, kanamycin, neomycin, netilmicin,

paromomycin, rhodostreptomycin,[2] streptomycin, tobramycin, and apramycin[3].

Systemic Aminoglycosides: Streptomycin Amikacin

Gentamicin Sisomicin

Kanamycin Netilmicin

Tobramycin

Topical Aminoglycosides:

Neomycin Framycetin

SRI SATYA SAI SCHOOL OF PHARMACY, SEHORE (M.P.)

Aminoglycoside

Mechanisms of action:

Aminoglycosides have several potential antibiotic mechanisms, some as protein synthesis

inhibitors, although their exact mechanism of action is not fully known:

They interfere with the proofreading process, causing increased rate of error in synthesis

with premature termination.[9]

Also, there is evidence of inhibition of ribosomal translocation where the peptidyl-tRNA

moves from the A-site to the P-site.[9]

They can also disrupt the integrity of bacterial cell membrane. [10]

They bind to the bacterial 30S ribosomal subunit[11][12] (some work by binding to the 50S

subunit[13])

There is a significant variability in the relationship between the dose administered and the

resultant plasma level in blood. Therapeutic drug monitoring (TDM) is necessary to obtain the

correct dose. These agents exhibit a post-antibiotic effect in which there is no or very little drug

level detectable in blood, but there still seems to be inhibition of bacterial re-growth. This is due

to strong, irreversible binding to the ribosome, and remains intracellular long after plasma levels

drop. This allows a prolonged dosage interval. Depending on their concentration, they act as

bacteriostatic or bactericidal agents.

The protein synthesis inhibition of aminoglycosides does not usually produce a bactericidal

effect, let alone a rapid one as is frequently observed on susceptible Gram-negative bacilli.

Aminoglycosides competitively displace cell biofilm-associated Mg2+ and Ca2+ that link the

polysaccharides of adjacent lipopolysaccharide molecules. "The result is shedding of cell

membrane blebs, with formation of transient holes in the cell wall and disruption of the normal

permeability of the cell wall. This action alone may be sufficient to kill most susceptible Gram-

negative bacteria before the aminoglycoside has a chance to reach the 30S ribosome." [14]

The antibacterial properties of aminoglycosides were believed to result from inhibition of

bacterial protein synthesis through irreversible binding to the 30S bacterial ribosome. This

explanation, however, does not account for the potent bactericidal properties of these agents,


Aminoglycoside

since other antibiotics that inhibit the synthesis of proteins (such as tetracycline) are not

bactericidal. Recent experimental studies show that the initial site of action is the outer bacterial

membrane. The cationic antibiotic molecules create fissures in the outer cell membrane, resulting

in leakage of intracellular contents and enhanced antibiotic uptake. This rapid action at the outer

membrane, it is presumed, accounts for most of the bactericidal activity. Energy is needed for

aminoglycoside uptake into the bacterial cell. Anaerobes have less energy available for this

uptake, so aminoglycosides are less active against anaerobes.

Aminoglycosides are useful primarily in infections involving aerobic, gram-negative bacteria,

such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some Mycobacteria,

including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. The most

frequent use of aminoglycosides is empiric therapy for serious infections such as septicemia,

complicated intraabdominal infections, complicated urinary tract infections, and nosocomial

respiratory tract infections. Usually, once cultures of the causal organism are grown and their

susceptibilities tested, aminoglycosides are discontinued in favor of less toxic antibiotics.

Streptomycin was the first effective drug in the treatment of tuberculosis, though the role of

aminoglycosides such as streptomycin and amikacin has been eclipsed (because of their toxicity

and inconvenient route of administration) except for multiple-drug-resistant strains.

Infections caused by gram-positive bacteria can also be treated with aminoglycosides, but other

types of antibiotics are more potent and less damaging to the host. In the past, the

aminoglycosides have been used in conjunction with beta-lactam antibiotics in streptococcal

infections for their synergistic effects, in particular in endocarditis. One of the most frequent

combinations is ampicillin (a beta-lactam, or penicillin-related antibiotic) and gentamicin. Often,

hospital staff refer to this combination as "amp and gent" or more recently called "pen and gent"

for penicillin and gentamicin.

Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi, and viruses.

Nonsense suppression:


Aminoglycoside

The interference with DNA proofreading has been exploited to treat genetic diseases that result

from premature stop codes (leading to early termination of protein synthesis and truncated

proteins). Aminoglycosides can cause the cell to overcome the stop code, insert a random amino

acid, and express a full-length protein. [15]

The aminoglycoside gentamicin has been used to treat cystic fibrosis (CF) cells in the laboratory

to induce them to grow full-length proteins. CF is caused by a mutation in the gene coding for

the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In approximately 10%

of CF cases, the mutation in this gene causes its early termination during translation, leading to

the formation of is truncated and non-functional CFTR protein. It is believed that gentamicin

distorts the structure of the ribosome-RNA complex, leading to a mis-reading of the termination

codon, causing the ribosome to "skip" over the stop sequence and to continue with the normal

elongation and production of the CFTR protein. [16]

Routes of administration

Since they are not absorbed from the gut, they are administered intravenously and

intramuscularly. Some are used in topical preparations for wounds. Oral administration can be

used for gut decontamination (e.g., in hepatic encephalopathy). Tobramycin may be administered

in a nebulized form.

Clinical use

The recent emergence of infections due to Gram-negative bacterial strains with advanced

patterns of antimicrobial resistance has prompted physicians to reevaluate the use of these

antibacterial agents. [17] This revived interest in the use of aminoglycosides has brought back to

light the debate on the two major issues related to these compounds, namely the spectrum of

antimicrobial susceptibility and toxicity. Current evidence shows that aminoglycosides do retain

activity against the majority of Gram-negative clinical bacterial isolates in many parts of the

world. Still, the relatively frequent occurrence of nephrotoxicity and ototoxicity during

aminoglycoside treatment makes physicians reluctant to use these compounds in everyday

practice. Recent advances in the understanding of the effect of various dosage schedules of


Aminoglycoside

aminoglycosides on toxicity have provided a partial solution to this problem, although more

research still needs to be done in order to overcome this problem entirely. [18]

Nomenclature

Aminoglycosides that are derived from bacteria of the Streptomyces genus are named with the

suffix -mycin, whereas those that are derived from Micromonospora are named with the suffix -

micin. [5]

This nomenclature system is not specific for aminoglycosides. For example, vancomycin is a

glycopeptide antibiotic and erythromycin, which is produced from the species

Saccharopolyspora erythraea (previously misclassified as Streptomyces) along with its synthetic

derivatives clarithromycin and azithromycin, is a macrolide. [7][8] All differ in their mechanisms

of action, however.

Streptomycin

Neomycin

Framycetin


http://en.wikipedia.org/wiki/File:Streptomycin3.svg

http://en.wikipedia.org/wiki/File:Neomycin.svg

http://en.wikipedia.org/wiki/File:Framycetin.png

http://en.wikipedia.org/wiki/File:Paromomycin.svg

Aminoglycoside

Paromomycin

Ribostamycin

Kanamycin

Amikacin

Arbekacin

Bekanamycin

Dibekacin


http://en.wikipedia.org/wiki/File:Ribostamycin.svg

http://en.wikipedia.org/wiki/File:Kanamycin_A.svg

http://en.wikipedia.org/wiki/File:Amikacin.svg

http://en.wikipedia.org/wiki/File:Arbekacin.png

http://en.wikipedia.org/wiki/File:Bekanamycin.png

http://en.wikipedia.org/wiki/File:Dibekacin.svg

Aminoglycoside

Tobramycin

Spectinomycin

Hygromycin B

Paromomycin sulfate

Gentamicin

Netilmicin


http://en.wikipedia.org/wiki/File:Tobramycin.svg

http://en.wikipedia.org/wiki/File:Spectinomycin.svg

http://en.wikipedia.org/wiki/File:Hygromycin_b.svg

http://en.wikipedia.org/wiki/File:Paromomycin.svg

http://en.wikipedia.org/wiki/File:Gentamicin_C2.svg

http://en.wikipedia.org/wiki/File:Netilmicin_structure.svg

Aminoglycoside

Sisomicin

Isepamicin

Verdamicin

Astromicin


http://en.wikipedia.org/wiki/File:Sisomicin.svg

http://en.wikipedia.org/wiki/File:Isepamicin.svg

http://en.wikipedia.org/wiki/File:Verdamicin.png

http://en.wikipedia.org/wiki/File:Astromicin.png

Aminoglycoside

Amikacin

Amikacin

Systematic (IUPAC) name

(2S)-4-amino-N-[(2S,3S,4R,5S)-5-amino-2-

[(2S,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-

6-(hydroxymethyl)oxan-2-yl]oxy-4-[(2R,3R,

4S,5R,6R)-6-(aminomethyl)-3,4,5-trihydroxy-

oxan-2-yl]oxy-3-hydroxy-cyclohexyl]-2-hydroxy-

butanamide

Clinical data

Trade names Amikin

AHFS/Drugs.com monograph

MedlinePlus a682661

Pregnancy cat. D(AU) C(US)

Legal status POM (UK) ℞-only (US)

Routes Intramuscular, intravenous


http://en.wikipedia.org/wiki/File:Amikacin.svg

Aminoglycoside

Pharmacokinetic data

Protein binding 0-11%

Half-life 2-3 hours

Excretion Renal

Identifiers

CAS number 37517-28-5

ATC code D06AX12 J01GB06, S01AA21

PubChem CID 37768

DrugBank APRD00550

ChemSpider 34635

UNII 84319SGC3C

KEGG D02543

ChEBI CHEBI:2637

ChEMBL CHEMBL177

Chemical data

Formula C22H43N5O13

Mol. mass 585.603 g/mol

SMILES eMolecules & PubChem

Amikacin is an aminoglycoside antibiotic used to treat different types of bacterial infections.

Amikacin works by binding to the bacterial 30S ribosomal subunit, causing misreading of

mRNA and leaving the bacterium unable to synthesize proteins vital to its growth.


Aminoglycoside

Administration

Amikacin may be administered once or twice a day but must be given by the intravenous or

intramuscular route. There is no oral form available as amikacin is not absorbed orally. In people

with kidney failure, dosage must be adjusted according to the creatinine clearance, usually by

reducing the dosing frequency.

Uses

Amikacin is most often used for treating severe, hospital-acquired infections with multidrug

resistant Gram negative bacteria such as Pseudomonas aeruginosa, Acinetobacter, and

Enterobacter. Serratia marcescens and Providencia stuartii are also included in the spectrum.

Amikacin can also be used to treat non tubercular mycobacterial infections and tuberculosis (if

caused by sensitive strains) when first line drugs fail to control the infection.

Amikacin may be combined with a beta-lactam antibiotic for empiric therapy for people with

neutropenia and fever.

Resistance

Amikacin has high resistance against bacterial inactivation. It resists attacks by most bacterial

inactivating enzymes, this is accomplished by the L-hydroxyaminobuteroyl amide (L-HABA)

moiety attached to N-3 which inhibits acetylation, phosphorylation and adenylation in the distant

amino sugar ring (C-2,C-3,C-4). To prevent the development of bacterial resistance to this

extremely powerful antibiotic, its use is tightly regulated.

Side effects

Side effects of amikacin are similar to other aminoglycosides. Kidney damage and hearing loss

are the most important effects. Because of this potential, blood levels of the drug and markers of

kidney function (creatinine) may be monitored. Moreover, doses are adjusted specifically based

upon serum Creatinine clearance in clinical settings.


Aminoglycoside

Apramycin

Apramycin


(2R,3R,4R,5S,6R)-5-amino-2- [((1R,2R,3R,4R,6R,8R)-8-amino-9- [(1R,2S,3R,4R,6R)-4,6-diamino-2,3- dihydroxy-cyclohexyl]oxy-2-hydroxy- 3-methylamino-5,10- dioxabicyclo[4.4.0]dec-4-yl)oxy]-6-

(hydroxymethyl)oxane-3,4-diol

Clinical data

AHFS/Drugs.com International Drug Names

Pregnancy cat. ?

Legal status ?

Identifiers


ATCvet code QA07AA92 QJ01GB90 QJ51GB90

PubChem CID 3081545

DrugBank DB04626

ChemSpider 2339128

UNII 388K3TR36Z

KEGG D02322

ChEBI CHEBI:2790


http://en.wikipedia.org/wiki/File:Apramycin.svg

Aminoglycoside

ChEMBL CHEMBL1230961

Chemical data

Formula C21H41N5O11



InChI[show]

Apramycin (also Nebramycin II) is an aminoglycoside antibiotic used in veterinary medicine. It

is produced by Streptomyces tenebrarius.

Pharmacology:

Indication

For the treatment of bacterial infections in animals.

Mechanism of action

Apramycin stands out among aminoglycosides for its mechanism of action which is based on

blocking translocation and its ability to bind also to the eukaryotic decoding site despite

differences in key residues required for apramycin recognition by the bacterial target. The drug

binds in the deep groove of the RNA which forms a continuously stacked helix comprising non-

canonical C.A and G.A base pairs and a bulged-out adenine. The binding mode of apramycin at

the human decoding-site RNA is distinct from aminoglycoside recognition of the bacterial target,

suggesting a molecular basis for the actions of apramycin in eukaryotes and bacteria.

Arbekacin


Aminoglycoside

Arbekacin


(2S)-4-amino-N-[(1R,2S,3R,4R,5S)-5-amino-2-{[(2S,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-6-

(hydroxymethyl)oxan-2-yl]oxy}-4-{[(2R,3R,6S)-3-amino-6-(aminomethyl)oxan-2-yl]oxy}-3-hydroxycyclohexyl]-

2-hydroxybutanamide

Clinical data

AHFS/Drugs.com International Drug Names

Pregnancy cat. ?

Legal status ℞ Prescription only



Metabolism Minimal

Excretion Renal


http://en.wikipedia.org/wiki/File:Arbekacin.png

Aminoglycoside

Identifiers


ATC code J01GB12

PubChem CID 11398765

DrugBank DB06696

ChemSpider 2140

UNII G7V6SLI20L

KEGG D07462

ChEMBL CHEMBL233430

Chemical data

Formula C22H44N6O10


Arbekacin (INN) is a semisynthetic aminoglycoside antibiotic. It is primarily used for the

treatment of infections caused by multi-resistant bacteria including methicillin-resistant

Staphylococcus aureus (MRSA), Arbekacin was originally synthesized from dibekacin in 1973.

It has been registered and marketed in Japan since 1990 under the trade name Habekacin.


Aminoglycoside

Arbekacin is no longer covered by patent and generic versions of the drug are also available

under such trade names as Decontasin and Blubatosine.

Pharmacology:

Indication

Arbekacin is used for the short term treatment of multi-resistant bacterial infections, such as

methicillin-resistant Staphylococcus aureus (MRSA).

Pharmacodynamics

Aminoglycosides, such as Arbekacin, work by binding to the bacterial 30S ribosomal subunit,

causing misreading of t-RNA which consequently, leaves the bacterium unable to synthesize

proteins vital to its growth. Energy is needed for aminoglycoside uptake into the bacterial cell.

Anaerobes have less energy available for this uptake, so aminoglycosides are less active against

anaerobes. Aminoglycosides are useful primarily in infections involving aerobic, gram-negative

bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter.

Mechanism of action

Aminoglycosides, such as 'Arbekacin, inhibit protein synthesis in susceptible bacteria by

irreversibly binding to bacterial 30S and 16S ribosomal subunits. Specifically Arbekacin binds to

four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with

decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region

interacts with the wobble base in the anticodon of tRNA. This leads to misreading of mRNA so

incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides

and the breakup of polysomes into nonfunctional monosomes.

Absorption


Aminoglycoside

Aminoglycosides are not well absorbed from the gastrointestinal tract. Their absorption is

markedly improved by parenteral administration.

Toxicity

Ototoxicity and nephrotoxicity are the most serious adverse effects of aminoglycoside therapy

and are more likely to occur in patients with a history of renal impairment or who are receiving

other ototoxic and/or nephrotoxic drugs. Normal duration of IM or IV aminoglycoside therapy is

7-10 days. Although a longer duration may be necessary in some cases, toxicity is more likely to

occur when aminoglycoside treatment is continued for longer than 10 days.

Affected organisms

Enteric bacteria and other eubacteria

Gentamicin

Gentamicin


http://en.wikipedia.org/wiki/File:Gentamicin_C2.svg

Aminoglycoside


(3R,4R,5R)-2-{[(1S,2S,3R,4S,6R)-4,6-

diamino-3-{[(2R,3R,6S)-

3-amino-6-[(1R)-

1-(methylamino)ethyl]oxan-2-yl]oxy}-

2-hydroxycyclohexyl]oxy}-5-methyl-

4-(methylamino)oxane-3,5-diol

Clinical data


MedlinePlus a682275

Pregnancy cat. D

Legal status POM (UK)

Routes IV, IM, topical


Bioavailability limited oral bioavailability

Protein binding 0-10%

Half-life 2 hrs

Excretion Renal


http://en.wikipedia.org/wiki/File:Gentamicin.png

Aminoglycoside

Identifiers


ATC code D06AX07 J01GB03 S01AA11 S02AA14 S03AA06 QA07AA91 QG01AA91 QG51AA04 QJ51GB03

PubChem CID 3467

IUPHAR ligand 2427

DrugBank DB00798

ChemSpider 390067

UNII T6Z9V48IKG

KEGG D08013

ChEBI CHEBI:27412

ChEMBL CHEMBL195892

Chemical data

Formula C21H43N5O7



InChI[show]

(what is this?) (verify)

Gentamicin is an aminoglycoside antibiotic, used to treat many types of bacterial infections,

particularly those caused by Gram-negative organisms. However, gentamicin is not used for

Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila. Gentamicin is also

ototoxic and nephrotoxic, with this toxicity remaining a major problem in clinical use.


Aminoglycoside

It is synthesized by Micromonospora, a genus of Gram-positive bacteria widely present in the

environment (water and soil). To highlight their specific biological origins, gentamicin and other

related antibiotics produced by this genus (verdamicin, mutamicin, sisomicin, netilmicin,

retymicin) generally have their spellings ending in ~micin and not in ~mycin. Gentamicin is a

bactericidal antibiotic that works by binding the 30S subunit of the bacterial ribosome,

interrupting protein synthesis.

Like all aminoglycosides, when gentamicin is given orally, it is not systemically active. This is

because it is not absorbed to any appreciable extent from the small intestine. It is administered

intravenously, intramuscularly or topically to treat infections. It appears to be completely

eliminated unchanged in the urine. Urine must be collected for many days to recover all of a

given dose because the drug binds avidly to certain tissues.

E. coli has shown some resistance to gentamicin, despite being Gram-negative. Reluctance to use

gentamicin for empirical therapy has led to increased use of alternative broad-spectrum

antibiotics, which some experts suggest has led to the prevalence of antibiotic-resistant bacterial

infections by Golden Staph and other so-called "superbugs".

Gentamicin is one of the few heat-stable antibiotics that remain active even after autoclaving,

which makes it particularly useful in the preparation of some microbiological growth media. It is

used during orthopaedic surgery when high temperatures are required for the setting of cements

(e.g. hip replacements).

Spectrum of activity

Active against a wide range of human bacterial infections, mostly Gram-negative bacteria

including Pseudomonas, Proteus, Serratia, and the Gram-positive Staphylococcus. Gentamicin is

not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila bacterial

infections (because of the risk of the patient going into shock from lipid A endotoxin found in


Aminoglycoside

certain Gram-negative organisms). Gentamicin is also useful against Yersinia pestis and its

relatives.

Side effects

These aminoglycosides are toxic to the sensory cells of the ear, but they vary greatly in their

relative effects on hearing versus balance. Gentamicin is a vestibulotoxin, and can cause

permanent loss of equilibrioception, caused by damage to the vestibular apparatus of the inner

ear, usually if taken at high doses or for prolonged periods of time, but there are well

documented cases in which gentamicin completely destroyed the vestibular apparatus after three

to five days. A small number of affected individuals have a normally harmless mutation in their

mitochondrial RNA (m1555 A>G), that allows the gentamicin to affect their cells. The cells of

the ear are particularly sensitive to this, sometimes causing complete hearing loss. However,

gentamicin is sometimes used intentionally for this purpose in severe Ménière's disease, to

disable the vestibular apparatus.

Gentamicin can also be highly nephrotoxic, particularly if multiple doses accumulate over a

course of treatment. For this reason gentamicin is usually dosed by body weight. Various

formulae exist for calculating gentamicin dosage. Also trough and peak serum levels of

gentamicin are monitored during treatment, generally before and after the third dose is infused.

Gentamicin, like other aminoglycosides, causes nephrotoxicity by inhibiting protein synthesis in

renal cells. This mechanism specifically causes necrosis of cells in the proximal tubule, resulting

in acute tubular necrosis which can lead to acute renal failure.

Side effects of gentamicin toxicity vary from patient to patient. Side effects may become

apparent shortly after or up to months after gentamicin is administered. Symptoms of gentamicin

toxicity include:

Balance difficulty

Bouncing, unsteady vision

Ringing in the ears (tinnitus)

Difficulty multi-tasking, particularly when standing


Aminoglycoside

Psychiatric symptoms related to gentamicin can occur. These include anorexia, confusion,

depression, disorientation and visual hallucinations. Immediate professional help should be

sought if any of these symptoms or others appear after administration of aminoglycosides.

General medical practitioners should refer patients with such symptoms to an otolaryngologist,

commonly known as an 'ear, nose, and throat doctor', for comprehensive tests.

A number of factors and determinants should be taken into account when using gentamicin,

including differentiation between empirical and directed therapy which will affect dosage and

treatment period. Many medical practitioners freely administer gentamicin as an antibiotic

without advising patients of the severe and permanent potential ramifications of its use.

Gentamicin is well known to be a cheap, low cost yet old medicine as compared to modern

alternatives, and is typically US$3–6 per dosage less than modern alternatives.

Many people recover from gentamicin toxicity naturally over time if the drug is discontinued,

but they recover slowly and usually incompletely. Sometimes the toxicity of gentamicin can still

increase over months after the last dose. Upon cessation of gentamicin therapy symptoms such as

tinnitus and imbalance may become less pronounced. Sensori-neural hearing loss caused by

gentamicin toxicity is permanent however.

Production and usage in research

Gentamicin is produced by a fermentation procedure. It was discovered by a Chinese

microbiologist, Yue Wang. The majority of the world's gentamicin production takes place in

China and South Korea; the last European producer is Lek, part of Sandoz group.

Gentamicin has been used since the early 1980s in microbiological research. The gentamicin

protection assay enables researchers to quantify the ability of pathogenic bacteria to invade

eukaryotic cells. It takes advantage of the fact that gentamicin is not able to penetrate eukaryotic

cells.


Aminoglycoside

Kanamycin

Kanamycin


2-(aminomethyl)- 6-[4,6-diamino-3- [4-amino-3,5-dihydroxy-6-(hydroxymethyl) tetrahydropyran-2-yl]oxy- 2-

hydroxy- cyclohexoxy]- tetrahydropyran- 3,4,5-triol

Clinical data


Pregnancy cat. D

Legal status ?

Routes Oral, intravenous, intramuscular


Bioavailability very low after oral delivery

Metabolism Unknown

Half-life 2 hours 30 minutes

Excretion Urine (as unchanged drug)

Identifiers


http://en.wikipedia.org/wiki/File:Kanamycin_A.svg

Aminoglycoside

CAS number 59-01-8

ATC code A07AA08 J01GB04 S01AA24

PubChem CID 6032

DrugBank APRD00026

ChemSpider 5810

UNII RUC37XUP2P

ChEBI CHEBI:17630

ChEMBL CHEMBL1384

Chemical data

Formula C18H36N4O11

Mol. mass 484.499


InChI[show]


Kanamycin sulfate is an aminoglycoside antibiotic, available in oral, intravenous, and

intramuscular forms, and used to treat a wide variety of infections. Kanamycin is isolated from

Streptomyces kanamyceticus.


Aminoglycoside

Mechanism

Kanamycin interacts with the 30S subunit of prokaryotic ribosomes. It induces substantial

amounts of mistranslation and indirectly inhibits translocation during protein synthesis.

Side effects

Serious side effects include tinnitus or loss of hearing, toxicity to kidneys, and allergic reactions

to the drug.

Use in research

Kanamycin is used in molecular biology as a selective agent most commonly to isolate bacteria

(e.g., E. coli) which have taken up genes (e.g., of plasmids) coupled to a gene coding for

kanamycin resistance (primarily Neomycin phosphotransferase II [NPT II/Neo]). Bacteria that

have been transformed with a plasmid containing the kanamycin resistance gene are plated on

kanamycin (50-100 ug/ml) containing agar plates or are grown in media containing kanamycin

(50-100 ug/ml). Only the bacteria that have successfully taken up the kanamycin resistance gene

become resistant and will grow under these conditions. As a powder kanamycin is white to off-

white and is soluble in water (50 mg/ml).

Mammalian cells and other eukaryotes are screened using G418, a similar aminoglycoside

antibiotic, which KanMX confers resistance against.

At least one such gene, Atwbc19 is native to a plant species, of comparatively large size and its

coded protein acts in a manner which decreases the possibility of Horizontal Gene Transfer from

the plant to bacteria; it may be incapable of giving resistance to kanamycin to bacteria even if

gene transfer occurs.


Aminoglycoside

Neomycin

Neomycin


(1R,2R,3S,4R,6S)-4,6-diamino-2-

Clinical data

Trade names Neo-rx


MedlinePlus a682274

Pregnancy cat. ?

Legal status OTC

Routes Topical, Oral



http://en.wikipedia.org/wiki/File:Neomycin_B_C.svg

Aminoglycoside

Half-life 2 to 3 hours

Identifiers


ATC code A01AB08 A07AA01, B05CA09, D06AX04, J01GB05, R02AB01,

S01AA03, S02AA07, S03AA01

PubChem CID 8378

IUPHAR ligand 709

DrugBank DB00994

ChemSpider 8075

UNII I16QD7X297

KEGG D08260

ChEBI CHEBI:7508

ChEMBL CHEMBL449118

Chemical data

Formula C23H46N6O13



InChI[show]


Aminoglycoside

Neomycin is an aminoglycoside antibiotic that is found in many topical medications such as

creams, ointments, and eyedrops. The discovery of Neomycin dates back to 1949. It was

discovered in the lab of Selman Waksman, who was later awarded the Nobel Prize in Physiology

and medicine in 1951. Neomycin, belongs to aminoglycoside class of antibiotics which contain

two or more aminosugars connected by glycosidic bonds. Neamine (two rings), Ribostamycin

(three rings), Paromomycin (four rings) and Lividomycin (five rings) are some other examples of

aminoglycosides. They have shown tremendous potential as antibacterials. One of them,

Gentamicin has been used extensively in clinical practice. Due to the inherent oto and

nephrotoxicity of these substances, systemic use has declined as safer alternatives have become

available.

Uses

Neomycin is overwhelmingly used as a topical preparation, such as Neosporin. It can also be

given orally, where it is usually combined with other antibiotics. Neomycin is not absorbed from

the gastrointestinal tract and has been used as a preventive measure for hepatic encephalopathy

and hypercholesterolemia. By killing bacteria in the intestinal tract, it keeps ammonia levels low

and prevents hepatic encephalopathy, especially prior to GI surgery. It has also been used to treat

small intestinal bacterial overgrowth. It is not given intravenously, as neomycin is extremely

nephrotoxic (causes kidney damage), especially compared to other aminoglycosides. The

exception is when neomycin is included, in very small quantities, as a preservative in some

vaccines - typically 0.025 mg per dose.

Molecular biology

Neomycin resistance is conferred by either one of two aminoglycoside phosphotransferase genes.

A neo gene is commonly included in DNA plasmids used by molecular biologists to establish

stable mammalian cell lines expressing cloned proteins in culture; many commercially available

protein expression plasmids contain neo as a selectable marker. Non-transfected cells will

eventually die off when the culture is treated with neomycin or similar antibiotic. Neomycin or

kanamycin can be used for prokaryotes, but geneticin (G418) is, in general, needed for

eukaryotes.


Aminoglycoside

Spectrum

Similar to other aminoglycosides, neomycin has excellent activity against Gram-negative

bacteria, and has partial activity against Gram-positive bacteria. It is relatively toxic to humans,

and many people have allergic reactions to it. See: Hypersensitivity. Physicians sometimes

recommend using antibiotic ointments without neomycin, such as Polysporin.

History

Neomycin was discovered in 1949 by the microbiologist Selman Waksman and his student

Hubert Lechevalier at Rutgers University. It is produced naturally by the bacterium

Streptomyces fradiae.

Neomycin as a DNA binder

Neomycin belongs to the family of aminoglycosides. This family includes many other

medicinally important drugs: streptomycin, paromomycin and kanamycin . Aminoglycosides are

known for their ability to bind to duplex RNA with high affinity. A study done by Daniel Pilch,

Associate Professor Dept. of Pharmacology at Rutgers University, and his coworkers determined

the association constant for neomycin with A-site RNA was found to be in the ~109 range.

However, more than 50 years after its discovery, its DNA-binding properties were still unknown.

In 2000, Dev P. Arya, currently Director of the Laboratory of Medicinal Chemistry at Clemson

University, and his coworkers discovered that neomycin induces enormous thermal stabilization

of triplex DNA while having little or almost no effect on the DNA duplex stabilization. They

also showed that neomycin binds to structures that adopt A-form structure, triplex DNA being

one of them. They later went on to show that neomycin even induces DNA:RNA hybrid triplex

formation.


Aminoglycoside

Netilmicin

Netilmicin


(2R,3R,4R,5R)-2-{[(1S,2S,3R,4S,6R)-4-amino-3-{[(2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-

yl]oxy}-6-(ethylamino)-2-hydroxycyclohexyl]oxy}-5-methyl-4-(methylamino)oxane-3,5-diol

Clinical data


MedlinePlus a605011

Pregnancy cat. ?

Legal status ?


Bioavailability ~0%

Half-life 2.5 hours

Identifiers


http://en.wikipedia.org/wiki/File:Netilmicin_structure.svg

Aminoglycoside


ATC code J01GB07 S01AA23

PubChem CID 41859

DrugBank APRD00232

ChemSpider 38195

UNII 4O5J85GJJB

KEGG D08268

ChEMBL CHEMBL1572

Chemical data

Formula C21H41N5O7



InChI[show]


Netilmicin is a member of the aminoglycoside family of antibiotics. These antibiotics have the

ability to kill a wide variety of bacteria. Netilmicin is not absorbed from the gut and is therefore

only given by injection or infusion. It is only used in the treatment of serious infections

particularly those resistant to gentamicin.


Aminoglycoside

Available dosage forms

Available dosage forms include:

UK: netilmicin (as Sulphate):

o 10 mg/mL (1.5 mL amp)

o 50 mg/mL (1-mL amp)

o 100 mg/mL(1-mL,1.5-mL & 2-mL amp)

France: Nétilmicin sulfate:

o Amp 25 mg/1 mL

o 50 mg/2 mL

o 100 mg/1 mL

o 150 mg/1.5 mL

Ingredients for 100 mg/mL vial

Netilmicin (as sulphate) 100 mg

Sodium metabisulfite 2.4 mg

Sodium sulfite 0.8 mg

Edetate disodium 0.1 mg

Benzyl alcohol 10 mg

Water for injection qs 1 mL

FDA approval date : February 28, 1983


Aminoglycoside

Comparison with drugs of the same therapeutic category:

According to the British National Formulary (BNF), netilmicin has similar activity to

gentamicin, but less ototoxicity in those needing treatment for longer than 10 days.Netilmicin is

active against a number of gentamicin-resistant Gram-negative bacilli but is less active against

Ps. Aeuroginosa than gentamicin or tobramycin.

However according to the below-mentioned studies, the above advantages are somehow

controversial:

Netilmicin (Netromycin, Schering-Plough, Netspan- Cipla):

In summary, netilmicin has not been demonstrated to have significant advantages over other

aminoglycosides (gentamicin, tobramycin, amikacin), and it is more expensive; thus, its

potential value is limited. Drug Intelligence & Clinical Pharmacy: Vol. 17, No. 2, pp. 83-91.

Once-daily gentamicin versus once-daily netilmicin in patients with serious infections—a

randomized clinical trial:

We conclude that with once-daily dosing no benefit of netilmicin over gentamicin regarding

nephro- or ototoxicity could be demonstrated. Journal of Antimicrobial Chemotherapy

(1994) 33, 823-835.

Ototoxicity and nephrotoxicity of gentamicin vs netilmicin in patients with serious

infections. A randomized clinical trial:

We conclude that with once-daily treatment no benefit of netilmicin over gentamicin

regarding nephro- or ototoxicity could be demonstrated. Clin Otolaryngol Allied Sci. 1995

Apr;20(2):118-23.

Relative efficacy and toxicity of netilmicin and tobramycin in oncology patients:

We conclude that aminoglycoside-associated ototoxicity was less severe and more often

reversible with netilmicin than with tobramycin. Arch Intern Med. 1986 Dec;146(12):2329-

34.


Aminoglycoside

Daily single-dose aminoglycoside administration. Therapeutic and economic benefits:

Animal studies have shown that dosing aminoglycosides once daily is more efficient and less

nephrotoxic than the conventional multiple daily dosing regimens. Netilmicin and amikacin

are the drugs most often used in clinical trials of once-daily dosing regimens. Ugeskr Laeger.

1993 May 10;155(19):1436-41.

Comparison of Netilmicin with Gentamicin in the Therapy of Experimental Escherichia coli

Meningitis:

Because of its reduced toxicity and greater in vivo bactericidal activity, netilmicin may offer

an advantage over gentamicin in the therapy of gram-negative bacillary meningitis.

Antimicrob Agents Chemother. 1978 June; 13(6): 899-904.

A comparison of netilmicin and gentamicin in the treatment of pelvic infections:

The microbacteria isolated by standard culture techniques before therapy revealed Neisseria

gonorrhoeae in 69% and 51% of the netilmicin and gentamicin groups, respectively;

anaerobic organisms were cultured in about 75% of each group. Obstetrics & Gynecology

1979;54:554-557.

Netilmicin: a review of toxicity in laboratory animals:

Presently available data suggest that netilmicin offers distinct advantages over older

aminoglycosides. Final conclusions must await prospective randomized double-blind trials in

man. J Int Med Res. 1978;6(4):286-99.

Nonparallel nephrotoxicity dose-response curves of aminoglycosides:

Nephrotoxicity comparisons of aminoglycosides in rats, utilizing large multiples of human

doses, have indicated an advantage for netilmicin. However, no nephrotoxicity advantage of

netilmicin has been demonstrated at the lower doses used in clinics. Antimicrob Agents

Chemother. 1981 June; 19(6): 1024–1028.

Comparative ototoxicity of netilmicin, gentamicin, and tobramycin in cats:

Under the conditions of this study, at least a twofold (vestibular) to fourfold (cochlear)

relative safety margin for ototoxicity was established in favor of netilmicin over tobramycin

and gentamicin. Toxicol Appl Pharmacol. 1985 Mar 15;77(3):479-89.


Aminoglycoside

Comparison of Netilmicin and Gentamicin Pharmacokinetics in Humans:

In a crossover study, single doses of netilmicin and gentamicin were administered

intramuscularly, each at 1.0 and 2.5 mg/kg. No significant differences were observed

between the two drugs in disposition half-life, rate of distribution and elimination, area under

the serum concentration-time curve, urinary excretion, total body clearance, and renal

clearance. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Feb. 1980, p. 184-187.

Schering-Plough Research Division, Bloomfield, New Jersey 07003.

Paromomycin sulfate

Paromomycin


(2R,3S,4R,5R,6S)-5-amino-6-[(1R,2S,3S,4R,6S)-

4,6-diamino-2-[(2S,3R,4R,5R)-4-[(2R,3R,4R,5R,6S)-

3-amino-6-(aminomethyl)-4,5-dihydroxy-oxan-2-yl]

oxy-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-

3-hydroxy-cyclohexyl]oxy-2-(hydroxymethyl)oxane-3,4-diol

Clinical data


http://en.wikipedia.org/wiki/File:Paromomycin_structure.svg

Aminoglycoside


MedlinePlus a601098

Pregnancy cat. B(US)

Legal status Rx only U.S.

Routes Oral, intramuscular


Bioavailability None

Metabolism None

Half-life ?

Excretion Fecal

Identifiers


ATC code A07AA06

PubChem CID 441375

DrugBank DB01421

ChemSpider 390117

ChEMBL CHEMBL370143

Chemical data


Aminoglycoside

Formula C23H47N5O18S



Paromomycin (brand name Humatin) is an aminoglycoside antibiotic, first isolated from

Streptomyces krestomuceticus in the 1950s. It is also called monomycin and aminosidine;

Uses

It is an antibiotic designed to fight intestinal infections such as cryptosporidiosis, amoebiasis,

and leishmaniasis.

The route of administration is intramuscular injection and capsule.

Mechanism

Paromomycin inhibits protein synthesis by binding to 16S ribosomal RNA.

History and availability

Paromomycin was demonstrated to be effective against cutaneous leishmaniasis in clinical

studies in the USSR in the 1960s, and in trials with visceral leishmaniasis in the early 1990s.

It was developed as a therapeutic against visceral leishmaniasis by the Institute for OneWorld

Health. Paromomycin was granted orphan drug status in 2005 and was approved by the Drug

Controller General of India in September 2006 for treatment of visceral leishmaniasis.

As of February 5th, 2008, King Pharmaceuticals is discontinuing the sale of Humatin.

Paromomycin continues to be available in the United States from another manufacturer.[9]

Streptomycin


Aminoglycoside

Streptomycin


5-(2,4-diguanidino-

3,5,6-trihydroxy-cyclohexoxy)- 4-[4,5-dihydroxy-6-(hydroxymethyl)

-3-methylamino-tetrahydropyran-2-yl] oxy-3-hydroxy-2-methyl

-tetrahydrofuran-3-carbaldehyde

Clinical data


Pregnancy cat. DM[1]

Legal status POM (UK) ℞-only (US)



Bioavailability 84% to 88% (est.)[2]


http://en.wikipedia.org/wiki/File:Streptomycin3.svg

http://en.wikipedia.org/wiki/File:Streptomycin-1ntb-xtal-3D-balls.png

Aminoglycoside

Half-life 5 to 6 hours

Excretion Renal

Identifiers

CAS number 57-92-1

ATC code A07AA04 J01GA01

PubChem CID 19649

DrugBank DB01082

ChemSpider 18508

UNII Y45QSO73OB

KEGG D08531

ChEBI CHEBI:17076

ChEMBL CHEMBL1201194

Chemical data

Formula C21H39N7O12



Physical data

Melt. point 12 °C (54 °F)


Streptomycin is an antibiotic drug, the first of a class of drugs called aminoglycosides to be

discovered, and was the first antibiotic remedy for tuberculosis. It is derived from the

actinobacterium Streptomyces griseus. Streptomycin is a bactericidal antibiotic. Streptomycin


Aminoglycoside

cannot be given orally, but must be administered by regular intramuscular injections. An adverse

effect of this medicine is ototoxicity.

Mechanism of action

Streptomycin is a protein synthesis inhibitor. It binds to the small 16S rRNA of the 30S subunit

of the bacterial ribosome, interfering with the binding of formyl-methionyl-tRNA to the 30S

subunit. This leads to codon misreading, eventual inhibition of protein synthesis and ultimately

death of microbial cells through mechanisms that are still not understood. Humans have

structurally different ribosomes from bacteria, thereby allowing the selectivity of this antibiotic

for bacteria. However at low concentrations Streptomycin only inhibits growth of the bacteria by

inducing prokaryotic ribosomes to misread mRNA. Streptomycin is an antibiotic that inhibits

both Gram-positive and Gram-negative bacteria, and is a therefore a useful broad-spectrum

antibiotic.

History

Streptomycin was first isolated on October 19, 1943 by Albert Schatz, a graduate student, in the

laboratory of Selman Abraham Waksman at Rutgers University. Dr. Waksman and his laboratory

discovered several antibiotics, including actinomycin, clavacin, streptothricin, streptomycin,

grisein, neomycin, fradicin, candicidin and candidin. Of these, streptomycin and neomycin found

extensive application in the treatment of numerous infectious diseases. Streptomycin was the

first antibiotic that could be used to cure the disease tuberculosis; early production of the drug

was dominated by Merck & Co. under George W. Merck.

The first randomized trial of streptomycin against pulmonary tuberculosis was carried out in

1946-1947 by the MRC Tuberculosis Research Unit under the chairmanship of Sir Geoffrey

Marshall (1887–1982). The trial was both double-blind and placebo-controlled. It is widely

accepted to have been the first randomised curative trial. Results showed efficacy against TB,

albeit with minor toxicity and acquired bacterial resistance to the drug.

Uses


Aminoglycoside

Treatment of diseases

Infective endocarditis caused by enterococcus when the organism is not sensitive to

Gentamicin

Tuberculosis in combination with other anti-TB drugs. It is not the first-line treatment,

except in medically under-served populations where the cost of more expensive treatments

are prohibitive.

Plague (Yersinia pestis) has historically been treated with it as the first-line treatment. It is

approved for this purpose by the U.S. Food and Drug Administration.

In veterinary medicine, streptomycin is the first-line antibiotic for use against gram negative

bacteria in large animals (horses, cattle, sheep etc.). It is commonly combined with procaine

penicillin for intramuscular injection.

While streptomycin is traditionally given intramuscularly (indeed, in many countries it is only

licensed to be used intramuscularly), the drug may also be administered intravenously.

Pesticide

Streptomycin is also used as a pesticide, to combat the growth of bacteria, fungi, and algae.

Streptomycin controls bacterial and fungal diseases of certain fruit, vegetables, seed, and

ornamental crops, and controls algae in ornamental ponds and aquaria. A major use is in the

control of fireblight on apple and pear trees. As in medical applications, extensive use can be

associated with the development of resistant strains.

Cell culture

Streptomycin, in combination with penicillin, is used in a standard antibiotic cocktail to prevent

bacterial infection in cell culture.

Tobramycin


Aminoglycoside

Tobramycin


(2S,3R,4S,5S,6R)-4-amino-2-{[(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2R,3R,5S,6R)-3-amino-6-(aminomethyl)-5-

hydroxyoxan-2-yl]oxy}-2-hydroxycyclohexyl]oxy}-6-(hydroxymethyl)oxane-3,5-diol

Clinical data

Trade names Tobrex


MedlinePlus a682660

Pregnancy cat. D (Injection, Inhalation); B (Ophthalmic) (US)

Legal status ?

Routes IV, IM, inhalation, ophthalmic



http://en.wikipedia.org/wiki/File:Tobramycin.svg

http://en.wikipedia.org/wiki/File:Tobramycin_1lc4.png

Aminoglycoside

Protein binding < 30%

Identifiers


ATC code J01GB01 S01AA12

PubChem CID 36294

DrugBank APRD00582

ChemSpider 33377

UNII VZ8RRZ51VK

KEGG D00063

ChEBI CHEBI:28864

ChEMBL CHEMBL1747

Chemical data

Formula C18H37N5O9



InChI[show]


Tobramycin is an aminoglycoside antibiotic used to treat various types of bacterial infections,

particularly Gram-negative infections.


Aminoglycoside

Mechanism of action

Tobramycin works by binding to a site on the bacterial 30S and 50S ribosome, preventing

formation of the 70S complex. As a result, mRNA cannot be translated into protein and cell

death ensues. Tobramycin is preferred over gentamicin for Pseudomonas aeruginosa pneumonia

due to better lung penetration and bactericidal activity.

Administration

Like all aminoglycosides, tobramycin does not pass the gastro-intestinal tract, so for systemic

use it can only be given intravenously, intramuscularly, eyedrops (commonly with

Dextramethsone), or it can be administered and inhaled via nebuliser. The formulation for

injection is branded Nebcin. Patients with cystic fibrosis will often take an inhalational

(nebulised) form (Tobi) for suppression of Pseudomonas aeruginosa infections. Tobramycin is

also combined with dexamethasone as an ophthalmic solution (TobraDex).

Bausch & Lomb Pharmaceuticals produces a sterile tobramycin solution (eye-drops) with a

tobramycin concentration of 0.3%, which is available by prescription only in the United States

and Canada. (In some countries, such as Italy, it is available over the counter.) It is mixed with

0.01% benzalkonium chloride as a preservative. These concentrations result in 3 mg per ml and

0.1 mg per ml, respectively.

A proprietary formulation of micronized, nebulized tobramycin has been tested as a treatment for

bacterial sinusitis.

Side effects

Like other aminoglycosides, tobramycin can cause deafness or a loss of equilibrioception

(vertigo) in genetically susceptible individuals. These individuals have a normally harmless

mutation in their DNA, that allows the tobramycin to affect their cells. The cells of the ear are

particularly sensitive to this.

Tobramycin can also be highly toxic to the kidneys, particularly if multiple doses accumulate

over a course of treatment.


Aminoglycoside

For these reasons, when tobramycin is given parenterally, it is usually dosed by body weight.

Various formulae exist for calculating tobramycin dosage. Also serum levels of tobramycin are

monitored during treatment.

References

1. ^ MeSH Aminoglycosides


Aminoglycoside

2. ^ "Bacterial 'battle for survival' leads to new antibiotic" (Press release). Massachusetts

Institute of Technology. February 26, 2008.

http://web.mit.edu/newsoffice/2008/antibiotics-0226.html. Retrieved December 1, 2010.

3. ^ Ryden, R; Moore (1977). "BJ". J Antimicrob Chemother 3 (6): 609–613.

4. ^ Kroppenstedt RM, Mayilraj S, Wink JM (Jun 2005). "Eight new species of the genus

Micromonospora, Micromonospora citrea sp. nov., Micromonospora echinaurantiaca sp.

nov., Micromonospora echinofusca sp. nov. Micromonospora fulviviridis sp. nov.,

Micromonospora inyonensis sp. nov., Micromonospora peucetia sp. nov.,

Micromonospora sagamiensis sp. nov., and Micromonospora viridifaciens sp. nov". Syst

Appl Microbiol. 28 (4): 328–39. PMID 15997706.

5. ^ Paul M. Dewick (2009). Medicinal Natural Products: A Biosynthetic Approach (3rd ed

ed.). Wiley. ISBN 0470741678.

6. ^ Walter P. Hammes1 and Francis C. Neuhaus (1974). On the Mechanism of Action of

Vancomycin: Inhibition of Peptidoglycan Synthesis in Gaffkya homari. 6. pp. 722–728.

7. ^ Protein synthesis inhibitors: macrolides mechanism of action animation. Classification

of agents Pharmamotion. Author: Gary Kaiser. The Community College of Baltimore

County. Retrieved on July 31, 2009

8. ^ The Mechanism of Action of Macrolides, Lincosamides and Streptogramin B Reveals

the Nascent Peptide Exit Path in the Ribosome Martin Lovmar and Måns Ehrenberg

9. ^ a b Pharmamotion --> Protein synthesis inhibitors: aminoglycosides mechanism of

action animation. Classification of agents Posted by Flavio Guzmán on 12/08/08

10. ^ Shakil, Shazi; Khan, Rosina; Zarrilli, Raffaele; Khan, Asad U. (2007).

"Aminoglycosides versus bacteria – a description of the action, resistance mechanism,

and nosocomial battleground". Journal of Biomedical Science 15 (1): 5–14.

doi:10.1007/s11373-007-9194-y. PMID 17657587.

11. ^ Levison, Matthew E. (July 2009). "Aminoglycosides: Bacteria and Antibacterial

Drugs". Merck Manual Professional.

http://www.merck.com/mmpe/sec14/ch170/ch170b.html.

12. ^ "Aminoglycosides". http://www.aic.cuhk.edu.hk/web8/aminoglycosides.htm.


Aminoglycoside

13. ^ Champney, W. S. (2001). "Bacterial Ribosomal Subunit Synthesis A Novel Antibiotic

Target". Current Drug Targets - Infectious Disorders 1 (1): 19–36.

doi:10.2174/1568005013343281. PMID 12455231.

14. ^ Lorian, Victor (1996). Antibiotics in Laboratory Medicine. Williams & Wilkins Press.

pp. 589–90. ISBN 0-683-05169-5.

15. ^ Feero, W. Gregory; Guttmacher, Alan E.; Dietz, Harry C. (2010). "New Therapeutic

Approaches to Mendelian Disorders". New England Journal of Medicine 363 (9): 852–

63. doi:10.1056/NEJMra0907180. PMID 20818846.

16. ^ Wilschanski, Michael; Yahav, Yaacov; Yaacov, Yasmin; Blau, Hannah; Bentur, Lea;

Rivlin, Joseph; Aviram, Micha; Bdolah-Abram, Tali et al. (2003). "Gentamicin-Induced

Correction of CFTR Function in Patients with Cystic Fibrosis andCFTRStop Mutations".

New England Journal of Medicine 349 (15): 1433–41. doi:10.1056/NEJMoa022170.

PMID 14534336.

17. ^ Falagas, Matthew E; Grammatikos, Alexandros P; Michalopoulos, Argyris (2008).

"Potential of old-generation antibiotics to address current need for new antibiotics".

Expert Review of Anti-infective Therapy 6 (5): 593–600. doi:10.1586/14787210.6.5.593.

PMID 18847400.

18. ^ Durante-Mangoni, Emanuele; Grammatikos, Alexandros; Utili, Riccardo; Falagas,

Matthew E. (2009). "Do we still need the aminoglycosides?". International Journal of

Antimicrobial Agents 33 (3): 201–5. doi:10.1016/j.ijantimicag.2008.09.001.

PMID 18976888.

External links

MedlinePlus drug information - Aminoglycosides (Systemic) Science Daily Bacterial 'Battle for Survival' - Rhodostreptomycin


aminoglycoside 2

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